PROJECT SUMMARY ? GENE EXPRESSION AND REGULATION The Gene Expression and Regulation Program (GER) is comprised of eight laboratories that work together in the areas of gene transcription and chromatin biology. The overarching goals of the Program match the long- term vision of the Cancer Center to merge basic understanding of fundamental biological mechanisms with translational identification of new, actionable therapeutic targets in cancer. To fulfill this goal, the GER Program brings together complementary and synergistic scientific excellence in three flagship themes: (i) Transcription and Chromatin Organization, (ii) Non-coding RNAs and Epigenetics, and (iii) Chromosomes and Genome Dynamics. In addition, the GER Program is at the forefront of an interdisciplinary theme in Chemical Biology of Novel Cancer Drug Targets, in line with the focus of the Cancer Center in early-stage academic drug discovery. Progress during the last five years has been transformative. GER Program members continued to lead their respective fields of investigation with high-impact publications in the top-tier literature, strengthened their cancer focus and attracted new talents to build ?critical mass? in flagship research themes. The most far-reaching goals set forth in the last Cancer Center Support Grant (CCSG) renewal were also met. GER Program members have now significantly expanded their intra- and inter-programmatic collaborations, increased the utilization of Shared Resources, achieved important basic and translational milestones in the ovarian cancer research continuum signature, and advanced innovative cancer therapeutics to the stage of first-in-human testing. During the last CCSG budget cycle, GER Program members published 104 cancer- related, discovery articles. Of these, 12.5% and 36.5% were the product of intra- or inter-programmatic collaborations, respectively, compared to 7% and 19% of the previous CCSG budget cycle, bringing the total collaborative publications of the Program from 23% in 2013 to more than 43% in 2018. Currently, GER Program members receive $3.4 million in peer-reviewed, cancer-related funding (total funding, $4.9 million), with $2.2 million from the NCI for a strong cancer focus of 64%. In addition, $2.2 million out of $3.4 million (65%) of peer-reviewed funding is the product of internal or external collaborations. Accordingly, the Program is home to two collaborative Program Project grants (P01 CA174439; P01 AG031862) and one multi- institutional Specialized Program of Research Excellence in ovarian cancer (SPORE, P50 CA228991; anticipated funding, 2018). In addition, the Program functions as a regional pole of collaborative research in early-stage drug discovery, leading a Philadelphia Drug Discovery Forum that brings together expertise from academic Institutions and the pharmaceutical and biotechnology industry. The GER Program is ideally poised to continue on this exponential trajectory of research preeminence during the next CCSG budget cycle, integrating basic understanding of biological pathways with impactful collaborations in translational cancer research.